Meilong Xu

Meilong Xu, Xiaoling Hu, Saumya Gupta et al.

In digital pathology, segmenting densely distributed objects like glands and nuclei is crucial for downstream analysis. Since detailed pixel-wise annotations are very time-consuming, we need semi-supervised segmentation methods that can learn from unlabeled images. Existing semi-supervised methods are often prone to topological errors, e.g., missing or incorrectly merged/separated glands or nuclei. To address this issue, we propose TopoSemiSeg, the first semi-supervised method that learns the topological representation from unlabeled histopathology images. The major challenge is for unlabeled images; we only have predictions carrying noisy topology. To this end, we introduce a noise-aware topological consistency loss to align the representations of a teacher and a student model. By decomposing the topology of the prediction into signal topology and noisy topology, we ensure that the models learn the true topological signals and become robust to noise. Extensive experiments on public histopathology image datasets show the superiority of our method, especially on topology-aware evaluation metrics. Code is available at https://github.com/Melon-Xu/TopoSemiSeg.

Chen Li, Xiaoling Hu, Shahira Abousamra et al.

Generative models, such as GANs and diffusion models, have been used to augment training sets and boost performances in different tasks. We focus on generative models for cell detection instead, i.e., locating and classifying cells in given pathology images. One important information that has been largely overlooked is the spatial patterns of the cells. In this paper, we propose a spatial-pattern-guided generative model for cell layout generation. Specifically, a novel diffusion model guided by spatial features and generates realistic cell layouts has been proposed. We explore different density models as spatial features for the diffusion model. In downstream tasks, we show that the generated cell layouts can be used to guide the generation of high-quality pathology images. Augmenting with these images can significantly boost the performance of SOTA cell detection methods. The code is available at https://github.com/superlc1995/Diffusion-cell.

Meilong Xu, Saumya Gupta, Xiaoling Hu et al.

Accurately modeling multi-class cell topology is crucial in digital pathology, as it provides critical insights into tissue structure and pathology. The synthetic generation of cell topology enables realistic simulations of complex tissue environments, enhances downstream tasks by augmenting training data, aligns more closely with pathologists' domain knowledge, and offers new opportunities for controlling and generalizing the tumor microenvironment. In this paper, we propose a novel approach that integrates topological constraints into a diffusion model to improve the generation of realistic, contextually accurate cell topologies. Our method refines the simulation of cell distributions and interactions, increasing the precision and interpretability of results in downstream tasks such as cell detection and classification. To assess the topological fidelity of generated layouts, we introduce a new metric, Topological Frechet Distance (TopoFD), which overcomes the limitations of traditional metrics like FID in evaluating topological structure. Experimental results demonstrate the effectiveness of our approach in generating multi-class cell layouts that capture intricate topological relationships. Code is available at https://github.com/Melon-Xu/TopoCellGen.

Meilong Xu, Xiaoling Hu, Shahira Abousamra et al.

In semi-supervised segmentation, capturing meaningful semantic structures from unlabeled data is essential. This is particularly challenging in histopathology image analysis, where objects are densely distributed. To address this issue, we propose a semi-supervised segmentation framework designed to robustly identify and preserve relevant topological features. Our method leverages multiple perturbed predictions obtained through stochastic dropouts and temporal training snapshots, enforcing topological consistency across these varied outputs. This consistency mechanism helps distinguish biologically meaningful structures from transient and noisy artifacts. A key challenge in this process is to accurately match the corresponding topological features across the predictions in the absence of ground truth. To overcome this, we introduce a novel matching strategy that integrates spatial overlap with global structural alignment, minimizing discrepancies among predictions. Extensive experiments demonstrate that our approach effectively reduces topological errors, resulting in more robust and accurate segmentations essential for reliable downstream analysis. Code is available at \href{https://github.com/Melon-Xu/MATCH}{https://github.com/Melon-Xu/MATCH}.

Wentao Huang, Meilong Xu, Xiaoling Hu et al.

Spatial transcriptomics (ST) provides essential spatial context by mapping gene expression within tissue, enabling detailed study of cellular heterogeneity and tissue organization. However, aligning ST data with histology images poses challenges due to inherent spatial distortions and modality-specific variations. Existing methods largely rely on direct alignment, which often fails to capture complex cross-modal relationships. To address these limitations, we propose a novel framework that aligns gene and image features using a ranking-based alignment loss, preserving relative similarity across modalities and enabling robust multi-scale alignment. To further enhance the alignment's stability, we employ self-supervised knowledge distillation with a teacher-student network architecture, effectively mitigating disruptions from high dimensionality, sparsity, and noise in gene expression data. Extensive experiments on seven public datasets that encompass gene expression prediction, slide-level classification, and survival analysis demonstrate the efficacy of our method, showing improved alignment and predictive performance over existing methods.

Qingqiao Hu, Weimin Lyu, Meilong Xu et al.

Whole Slide Image (WSI) understanding is fundamentally challenging due to its gigapixel scale and the extreme sparsity of diagnostically relevant regions. Unlike human experts who primarily rely on key areas to arrive at a diagnosis, existing slide-level multimodal large language models (MLLMs) for pathology rely on heavy slide-level encoders that process thousands of patch features in a brute-force manner, resulting in excessive computational cost. In this work, we revisit the WSI-language modeling paradigm and show that tile-level features exhibit strong global and local redundancy, whereas only a small subset of tiles are truly task-relevant. Motivated by this observation, we introduce an efficient MLLM framework, called LoC-Path, that replaces the expensive slide-level encoder with redundancy-reducing modules. We first design a Sparse Token Merger (STM) and an MAE-pretrained resampler to remove local redundancy and compress globally redundant tile tokens into a compact slide-level representation set. We then propose a Cross-Attention Routing Adapter (CARA) and a Token Importance Scorer (TIS) to integrate the compressed visual representation with the language model in a computation-efficient manner. Extensive experiments demonstrate that our approach achieves performance comparable to existing state-of-the-art whole-slide MLLMs, while requiring significantly lower computation and memory.

Jiamu Bai, Xin Yu, Meilong Xu et al.

Reinforcement learning from human feedback (RLHF) has proven effectiveness for aligning text-to-image (T2I) diffusion models with human preferences. Although Direct Preference Optimization (DPO) is widely adopted for its computational efficiency and avoidance of explicit reward modeling, its applications to diffusion models have primarily relied on pairwise preferences. The precise optimization of listwise preferences remains largely unaddressed. In practice, human feedback on image preferences often contains implicit ranked information, which conveys more precise human preferences than pairwise comparisons. In this work, we propose Diffusion-LPO, a simple and effective framework for Listwise Preference Optimization in diffusion models with listwise data. Given a caption, we aggregate user feedback into a ranked list of images and derive a listwise extension of the DPO objective under the Plackett-Luce model. Diffusion-LPO enforces consistency across the entire ranking by encouraging each sample to be preferred over all of its lower-ranked alternatives. We empirically demonstrate the effectiveness of Diffusion-LPO across various tasks, including text-to-image generation, image editing, and personalized preference alignment. Diffusion-LPO consistently outperforms pairwise DPO baselines on visual quality and preference alignment.